Molecular effects of Staphylococcus aureus toxins and their contribution to pathogenesis

Abstract

The gram-positive bacterium Staphylococcus aureus (S.aureus) is carried by up to 30% of the population and can cause disease, including skin and soft tissue infections. But also more severe symptoms like abscesses, sepsis and pneumonia were described. In the past, pathogenic S.aureus strains were mainly present in hospitals. However, since the beginning of the 1990s S.aureus strains emerged which can also be found outside of hospitals. The success of such community-associated strains is based on a high expression of a broad variety of virulence factors including genes for antibiotic resistance and exotoxins. Such exotoxins can be subdivided into three groups: The first group consists of hemolysins which have the ability to lyze blood cells, namely erythrocytes, phagocytes and lymphocytes. This effect is based on the formation of pores in the membrane of the affected cell, which disturbs the ion metabolism and results in depletion of small molecules like ATP. Lysis of erythrocytes could hereby help S.aureus to attain iron out of the erythrocyte-derived proteins hemoglobin and myoglobin. Lysis of immune cells could provide a mechanism of immune evasion, since phagocytes and lymphocytes are required for an efficient clearance of S.aureus infections. The second group comprises the superantigens. Staphylococcal superantigens cross-link Vβ chains of distinct T-cell receptor variants present on CD4+ T cells with major histocompatibility complex (MHC) class II molecules of professional antigen presenting cells (APC). This cross-linking does not require antigen specifity of the MHC class II molecules and can result in activation in up to 20% of the overall T cell population. T cell activation is followed subsequently by anergy and depletion of the respective T cell clones, which could facilitate S.aureus infections because T cells play an important role in clearance of bacterial infections. The third group is the group of exfoliative toxins, which can cause proteolytic cleavage of the cadherin desmoglein-1 (Dsg1). Dsg1 is responsible for cell-cell interactions within the skin and its cleavage results in disruption of the skin barrier. The disruption of the skin barrier was described to be an important factor for a successful establishment of an infection by S.aureus. Taken together, the described staphylococcal exotoxins are important virulence factors enhancing the ability of S.aureus to establish and maintain an infection. Although hemolysins, superantigens and exfoliative toxins require further investigations to determine the impact of the toxins more in detail, this knowledge could be used in the future to develop drugs and vaccines for the treatment or prevention of S.aureus infections.